Study record

MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner

Gudiksen A, Hansen CC, van der Stede T et al. · Free Radic Biol Med · 2026

AnimalSeveralEvidence tier CAlso: Human observationalAlso: Analytical / methods

What this study reported

Reported that administered MOTS-c was associated with greater skeletal muscle mitochondrial bioenergetic performance in two transgenic mouse strains, with the association depending on both PGC-1α and AMPK. Found no apparent change in mitochondrial respiratory protein content but lower mitochondrial reactive oxygen species emission and less ROS-related protein damage in mouse muscle, with RNA-sequencing pointing to changes in redox handling, mitochondrial integrity and OXPHOS efficiency. Measured no change in arterio-venous difference during one-legged knee extensor exercise in humans despite higher interstitial MOTS-c.

Limitations

Group sizes and participant numbers are not reported in the abstract, the mouse work relies on two genetically modified strains with no sex breakdown given, and the human arm is a small acute exercise measurement without a control condition.

Study record

Annotated fields for this study
Study modelAnimal study (in vivo)
Substance studiedSeveralMore than one of these is central to the paper (common for reviews).
Speciesmouse, human
System studiedTwo transgenic mouse strains lacking PGC-1α or AMPK signalling in skeletal muscle; humans performing one-legged knee extensor exercise
Populationadults performing one-legged knee extensor exercise
DesignControlled animal experiment in transgenic strains with an accompanying human exercise measurement study
Sample size as reportedNot reported
Control groupuntreated transgenic and wild-type mice
Route (data field only)Not reported
Endpoints measuredskeletal muscle mitochondrial bioenergetic performance; mitochondrial respiratory protein content; mitochondrial reactive oxygen species emission and ROS-related protein damage; muscle RNA-sequencing profile; arterio-venous difference in interstitial MOTS-c during exercise
Pathways measuredAMPK signalling · SIRT1 / PGC-1α / biogenesis · Oxidative stress
Research areasSkeletal muscle · Mitochondrial biology · Exercise
Evidence tierC — Animal in vivo
Publication typesJournal Article

Appraisal

Each dimension is recorded separately and never combined into a single score. A study can be well controlled and still tell you little about people.

Relevance to MOTS-c
Direct
Model applicability
Mammalian
Sample size
Not reported
Controls
Appropriate
Outcome validity
Surrogate
Support for its own conclusion
Moderate

Provenance

  • Bibliographic fields retrieved from PubMed E-utilities efetch (title, journal, date, authors, DOI) on 2026-11-11.
  • Annotated from the published abstract.
  • Editorial review: approved (2026-11-11).
  • Classification follows the site methodology; the record describes the study, not what MOTS-c does in people.